Details of the Drug

General Information of Drug (ID: DM0Q7NO)

Drug Name
AMG 176
Synonyms
JQNINBDKGLWYMU-GEAQBIRJSA-N; AMG-176; 1883727-34-1; AMG176; SCHEMBL17550216; EX-A2666; HY-101565; CS-0021721; Spiro[5,7-etheno-1H,11H-cyclobut[i][1,4]oxazepino[3,4-f][1,2,7]thiadiazacyclohexadecine-2(3H),1'(2'H)-naphthalen]-8(9H)-one, 6'-chloro-3',4',12,13,16,16a,17,18,18a,19-decahydro-16-methoxy-11,12-dimethyl-,10,10-dioxide, (1'S,11R,12S,14E,16S,16aR,18aR)-
Indication
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Phase 1 [1]
Multiple myeloma 2A83 Phase 1 [2]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 613.2
Logarithm of the Partition Coefficient (xlogp) 6.8
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C33H41ClN2O5S
IUPAC Name
(3'R,4S,6'R,7'S,8'E,11'S,12'R)-7-chloro-7'-methoxy-11',12'-dimethyl-13',13'-dioxospiro[2,3-dihydro-1H-naphthalene-4,22'-20-oxa-13lambda6-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16(25),17,19(24)-tetraene]-15'-one
Canonical SMILES
C[C@H]1C/C=C/[C@@H]([C@@H]2CC[C@H]2CN3C[C@@]4(CCCC5=C4C=CC(=C5)Cl)COC6=C3C=C(C=C6)C(=O)NS(=O)(=O)[C@@H]1C)OC
InChI
InChI=1S/C33H41ClN2O5S/c1-21-6-4-8-30(40-3)27-12-9-25(27)18-36-19-33(15-5-7-23-16-26(34)11-13-28(23)33)20-41-31-14-10-24(17-29(31)36)32(37)35-42(38,39)22(21)2/h4,8,10-11,13-14,16-17,21-22,25,27,30H,5-7,9,12,15,18-20H2,1-3H3,(H,35,37)/b8-4+/t21-,22+,25-,27+,30-,33-/m0/s1
InChIKey
JQNINBDKGLWYMU-GEAQBIRJSA-N
Cross-matching ID
PubChem CID
118910268
CAS Number
1883727-34-1
TTD ID
D0I5DP
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) TTL53M6 MCL1_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Post-Translational Modifications [3]
E3 ubiquitin-protein ligase HUWE1 (HUWE1) OTFH6BJS HUWE1_HUMAN Gene/Protein Processing [3]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Post-Translational Modifications [3]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [3]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [3]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Gene/Protein Processing [3]
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (INPPL1) OTCDAVBQ SHIP2_HUMAN Gene/Protein Processing [3]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Acute myeloid leukaemia
ICD Disease Classification 2A60
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) DTT MCL1 1.06E-04 1.29 2.97
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT03797261) A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies. U.S. National Institutes of Health.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies. Clin Cancer Res. 2023 Jan 17;29(2):446-457. doi: 10.1158/1078-0432.CCR-22-2088.